Sefpime

Sefpime

cefepime

Manufacturer:

Sinopharm Zhijun (Shenzhen)

Distributor:

S Charoen Bhaesaj Trading
Full Prescribing Info
Contents
Cefepime hydrochloride.
Description
Each vial contains Cefepime HCl for injection equivalent to 1.0 g of Cefepime.
Action
Pharmacology: Pharmacodynamics: Cefepime is a fourth-generation broad-spectrum bactericidal agent that acts by inhibition of bacterial cell wall synthesis. It is against both Gram-positive and Gram-negative bacteria. Highly resistant to hydrolysis by a number of β-lactamases, it has a low affinity for chromosomally encoded β-lactamases, and exhibits rapid penetration into Gram-negative bacterial cells.
Cefepime has been shown to be active against the following organisms: Gram-negative aerobes: Enterobacter spp., K. pneumoniae, E. coli, Proteus mirabilis, B.pyocyaneus, Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa.
Gram-positive aerobes: Staphylococcus aureus (only methicillin-susceptible strains), Streptococcus pyogenes (Group A), Streptococcus pneumoniae, Viridans streptococci, Staphylococcus epidermidis, Group B Streptococcus agalactiae.
Anaerobic organisms: Bacteroides fragilis.
Most Enterococci like Enterococcus faecalis and methicillin-resistant staphylococci are resistant to Cefepime.
Pharmacokinetics: Cefepime is fitted to linear dynamic model in-vivo when a single dosage of 0.25g~2g is intravenously given. There is no evidence of accumulation in healthy male volunteers receiving therapeutic dosages for a period of 9 days.
The serum protein binding rate is about 20% and is independent of drug concentration in the serum. The average steady distribution volume is 13-22 L. Therapeutic concentrations are found in urine, bile, peritoneal fluid, blister fluid, bronchial mucosa, sputum, prostate, appendix and gallbladder. It can penetrate infectious blood-brain barrier.
The average plasma elimination half-life time is 2.0±0.3 hours, the total clearance rate is 120.0±8.0ml/min. Cefepime is mainly eliminated by renal secretion. Only a small part can be transformed to NMP (N-methylpyrrolidine) and metabolized as NMP-N-oxide in the body. In the urine unchanged cefepime represents approximately 80-82% of dose, less than 1% of NMP, 6.8% of NMP-N-oxide and 2.5% of cefepime isomer.
After those aged 2 months up to 11 years are intravenously given single dosage of 50 mg/kg of cefepime, the total clearance and steady distribution volume is 3.3±1.0ml/min/kg and 0.3±0.1L/kg, respectively. In the urine unchanged cefepime represents approximately 60% of dose. The average renal clearance is 2.0ml/min/kg. There is no difference of clearance and distribution volume between sex and age among children. There is no evidence of accumulation in those children when they are given cefepime at a dose of 50mg/kg q12h. When cefepime is given q8h the steady Cmax, AUC and half-life increase approximately 15%.
Toxicology: Genotoxicity: Not established by in-vitro and in-vivo studies.
Reproductive toxicity: Mice, rats and rabbits were given 1200, 1000 and 100mg/kg of cefepime respectively (equivalent to 1~4 times the maximum dosage in human on the basis of body surface area), no evident toxicity was shown. But the correlation between animals and humans is still uncertain. The studies on pregnant women are no sufficient.
Indications/Uses
It is indicated in the treatment of infections caused by susceptible bacteria, for adults and children aged 2 months up to 16 years.
Lower respiratory tract infections; urinary tract infections; skin and skin structure infections; intra-abdominal infections; empiric treatment in febrile neutropenia; gynecologic and obstetric infections; septicemia; bacterial meningitis in children.
Culture and susceptibility studies should be performed to determine susceptibility of the causative organisms to cefepime.
Dosage/Direction for Use
For adults and children of 40kg or >40kg: 1~2g/time, q12h, IV for 7~10 days.
For mild or moderate urinary tract infections, 0.5~1g/time, q12h, IV for 7~10 days.
For severe urinary tract infections, 2g/time, q12h, IV for 10 days.
For empirical treatment in febrile neutropenia complicated with fever, IV 2g/time, q8h, for 7~10 days or until neutropenia is controlled. If the fever is brought down while the level of neutrophilic granulocytes is till abnormally low, the use of antibiotic should be re-evaluated. The maximum dose for children of 2 months up to 12 years of age should not exceed that of adults (2g/time). Children >40kg may use dose of adults, usually 50mg/kg, IV q12h for 7~14 days; for neutropenic children, 50mg/kg, q8h.
Experience with the use of cefepime in pediatric patients <2 months of age is limited, while this experience attained in patients >2 months of age suggested that a dosage of 100-150 mg/kg daily divided in 3 dose, a dosage of 30 mg/kg q12h or q8h may be considered for patients aged 1 month up to 2 months with careful monitoring.
Adjustment in dosage is not necessary in patients with impaired hepatic function.
For patients with impaired renal function, the initial dose of cefepime is the same as in patients with normal renal function. The recommended doses of cefepime in patients with renal insufficiency are presented in the following table: see Table.

Click on icon to see table/diagram/image

The data of use of cefepime in children with impaired renal function is not available. Due to similar pharmacokinetics between children and adults, the dosage for adults with renal impairment is recommended for children with renal impairment.
Administration: For direct IV injection, the 1g vial should be constituted with 10 ml of Sterile Water for Injection, 5% Dextrose Injection or 0.9% Sodium Chloride Injection. The resulting solution should be injected directly into the vein over a period of 3-5 min or injected into the tubing of an administration set while the patient is receiving a compatible IV fluid.
For IV infusion, the 1g vial should be constituted as noted previously for direct IV Injection, then add the appropriate quantity of the resulting solution to an IV container with one of the following compatible IV fluids to obtain solutions with concentrations between 1 and 40 mg/ml: 0.9% Sodium Chloride Injection, 5% and 10% Dextrose Injection, M/6 Sodium Lactate Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, Lactated Ringer's and 5% Dextrose Injection.
These solutions are stable for 24 hours when stored at room temperature (<25°C ) or 7 days when stored under refrigeration (2~8°C).
Overdosage
Symptoms include neuromuscular hypersensitivity and convulsions. Many beta-lactam antibiotics have the potential to cause neuromuscular hyperirritablity or seizures. Hemodialysis may be helpful to aid in the removal of the drug from the blood, however, most often treatment is supportive and symptom directed.
Contraindications
The use of cefepime in those who are allergic to cefepime or L-arginine, cephalosporins, penicillin and β-lactam antibiotics is forbidden.
Warnings
Cefepime is contraindicated in patients with known hypersensitivity to this medication.
The patients who are allergic to Penicillin may also have severe reactions resulted in the patient's death.
Discontinue the medication and consult the doctor or pharmacist when the following symptoms occur e.g. fever, rash, blister, skin and mucous membrane detachment e.g. oral cavity, pharynx, nasal, genitals and conjunctivitis.
Special Precautions
Before use, make sure that the patients have no any allergic history to cefepime, other cephalosporins drugs, penicillin or other β-lactam antibiotics. Or they should be used with great care.
Broad-Spectrum antibiotics will induce pseudomembranous enteritis. In the case of diarrhea during the treatment with cefepime, the possibility of pseudomembranous enteritis should be considered. Stop administration for mild enteritis and special treatment for moderate to severe enteritis. It should be used with caution when prescribe cefepime to those with gastro-intestinal diseases, especially enteritis sufferers.
Similar to other cephalosporins, cefepime may cause decreased prothrombin activity. Prothrombin time should be monitored on the patients having the risk factors decreasing prothrombin activity, such as those with liver, renal insufficiency and malnutrition, and prolonged antibacterial treatment. If necessary, exogenous vitamin K should be administered.
When dosage administered is 33 times the maximum recommended dosage, arginine included in this product will cause glucose metabolic disorder and transient increase in blood potassium; while the influence of arginine is not definite when the dosage is smaller.
Dosage and administration interval should be adjusted for patients with renal insufficiency (elimination rate of creatinine ≤60ml/min).
When used concurrently with aminoglycosides drugs or strong diuretics, it should strengthen the clinical observation and monitor patients' renal functions to avoid triggering the nephrotoxicity or ototoxicity induced by aminoglycosides.
Nervous system effects that have occurred include dizziness, headache, malaise, fatigue, nightmares, vertigo, seizures, encephalopathy, myoclonus.
Use in Children: Cefepime should not be used in pediatric patients of any age for the treatment of serious infections that are suspected or known to be caused by Haemophilus influenzae type B. Safety and efficacy of Cefepime in children younger than 2 months of age have not been established.
Use in the Elderly: The elderly patients with normal renal function should use generally recommended dosage and the effectiveness and safety are the same with the adult. Adjustment in dosage and administration should be needed in the elderly patients with renal insufficiency.
Use In Pregnancy & Lactation
Although animal reproductive toxicity test and teratogenicity test show that cefepime has no teratogenicity and embryotoxicity, there's no sufficient and well-contrasting clinical data on pregnant and breast feeding women. So pregnant women should use with great care.
Cefepime is distributed into milk (with the concentration of about 0.5μg/ml). So it should be used with caution when using this product on breast feeding women.
Adverse Reactions
The most common side effects are mild and transient: Diarrhea, skin rash and local reaction at injection site such as phlebitis, pain or inflammation. Other effects are nausea, vomiting, anaphylaxis, pruritus, fever, paraesthesia and headache.
Enteritis (including pseudomembranous enteritis) and oral candidiasis are occasionally reported.
Abnormal laboratory tests are almost transient, and will recover upon withdrawal, including increase in transaminase (ALT and/or AST), alkaline phosphatase concentration have occurred occasionally, serum concentration of bilirubin, decrease serum albumin and/or total protein have been reported. Hepatic dysfunction, including cholestasis, also have been reported.
Renal effects that have occurred occasionally with administration of a cephalosporin include transient increases in BUN and serum creatinine concentrations, renal dysfunction and toxic nephropathy.
Hematologic effects include rare, mild and transient neutropenia, thrombocytopenia, leukocytosis, granulocytosis, aplastic anemia, hemolytic anemia, and hemorrhage, prolonged partial thromboplastin time and prothrombin time.
Cephalosporins will also cause Stevens-Johnson syndrome, multiform erythemia, toxic epidermal necrosis.
Hypersensitivity: Rash, pruritus.
Central nervous system: Fever, headache, seizures. If seizures occur during cefepime therapy, the drug should be discontinued.
Drug Interactions
When used concurrently with aminoglycosides drugs or strong diuretics, it should strengthen the clinical observation and monitor patients' renal functions to avoid triggering the nephrotoxicity or ototoxicity induced by aminoglycosides.
Storage
Protect from light, tightly closed in a cool and dry place at a temperature not exceeding 25°C.
MIMS Class
ATC Classification
J01DE01 - cefepime ; Belongs to the class of fourth generation cephalosporins. Used in the systemic treatment of infections.
Presentation/Packing
Inj (vial) 1 g (white to pale yellow powder) x 10 x 1's.
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